The adverse effects of alcohol consumption are dependent on the amount and rate of consumption as well as genetic and physiological conditions that vary between individuals. The symptoms of a hangover are the delayed indications of the physiological effects of excessive alcohol consumption and can include headaches, sensitivity to sound and light, fatigue, and nausea.
The physiological effects of alcohol consumption include vasodilation (followed later by vasoconstriction), decreased blood oxygen concentration, increased oxygen demand, imbalanced internal pH level, increased carbon dioxide concentration, dehydration, loss of electrolytes, inhibited enzymatic and metabolic activities, excess energy transfer molecules, particularly NADH and ATP, and accumulation of toxic metabolic by-products, particularly Acetaldehyde and its adducts.
Ingested alcohol is absorbed into the blood stream by the stomach and the small intestines. Once in the circulatory system, alcohol triggers the movement of water and electrolytes across the vascular cell membranes into the bloodstream. The movement of electrolytes, especially calcium, out of vascular cells interferes with the myogenic control of blood vessel diameter. The movement of excess water into the bloodstream creates a condition of low blood electrolyte concentration that triggers the release of antidiuretic hormone, also called vasopressin. Vasopressin would normally have a constrictive effect on the blood vessels, but this effect is inhibited by the conditions created by alcohol and its metabolic by-products. The result is dilated blood vessels and a net loss of fluid and electrolytes.
The release of vasopressin continues as long as the concentration of electrolytes remains low and the inhibitory signal is absent. The result is an accumulation of vasopressin that leads to over constriction of blood vessels when the concentrations of alcohol and its metabolic by-products eventually fall. The severity of the constrictive effect of accumulated vasopressin on the diameter of blood vessels varies with location, the concentration of free calcium ions, and the time period of alcohol consumption. Cerebral and coronary arteries are especially vulnerable to excessive vasoconstriction which is also affected by pH levels and carbon dioxide and oxygen concentrations.
Four main enzymes are involved in the metabolism of ethanol: Alcohol Dehydrogenase (“ADH”), Acetaldehyde Dehydrogenase (“ALDH”), Cytochrome P450 (“CYP2E1”), and Catalase.
In most people, the majority of ingested alcohol is metabolized in the liver by ADH into acetaldehyde, a highly reactive by-product that is 20 to 30 times more toxic than alcohol. Acetaldehyde is further metabolized in the mitochondria into acetic acid by ALDH. Acetic acid readily converts to acetate, when the pH is above 5.5. Continuous mitochondrial oxidation of acetaldehyde into acetic acid leads to a build up of acetates and, consequently, to excess acetaldehyde that crosses mitochondrial and cell membranes into the blood stream.
Acetaldehyde has the capacity to form adducts with amino acids, proteins, nucleic acids, enzymes, co-enzymes, and other biomolecules and hinder their activity. Among the most susceptible proteins are hemoglobin and cytochromes, both of which are critically important in the metabolism of alcohol, sugar, proteins, and fats. Acetaldehyde-hemoglobin adducts reduce the affinity of oxygen to hemoglobin, resulting in a decreased oxygen loading. Further, alkaline conditions created by alcohol metabolism increase the affinity of oxygen to free hemoglobin, thereby decreasing the unloading of oxygen. The decreased availability of oxygen leads to the downregulation of the electron transport chain.
During alcohol metabolism there is an increased demand for oxygen. In addition, when the concentrations of alcohol or its by-products are high, Kupffer cells become activated. Their activation releases stimulatory molecules that increase the metabolic activity of hepatocytes. As a result, oxygen demand by cells increases even further and hypoxia and cell death are increased.
Alcohol consumption also leads to the inhibition of carbon dioxide binding to hemoglobin, which downregulates its elimination and leads to increased carbon dioxide concentrations. Excess carbon dioxide reacts with water to produce carbonic acid and hydrogen ions, thereby contributing to a decrease in pH and a risk of carbonic acidosis.
As acetaldehyde continues to accumulate it is converted to acetyl-CoA. Excess acetyl-CoA contributes to a drop in cellular pH by being converted into ketones and contributing to the accumulation of acetic acid and pyruvate, which is converted to lactic acid.
The oxidation of alcohol and acetaldehyde by ADH and ALDH produces an excess of NADH molecules while depleting NAD+. This decreases the ratio of NAD+/NADH, thereby reducing the redox potential of hepatic cells. Excess NADH also contributes to the inhibition of both the citric acid cycle (the “Kreb cycle”) and the urea cycle. The downregulation of the Kreb cycle results in an increase in the concentration of acetyl-CoA and subsequent downregulation of the enzyme pyruvate dehydrogenase. The electron transport chain (“ETC”) helps decrease the concentration of NADH by the production of ATP and water. The normal functioning of the ETC relies on the availability of oxygen. Both a decrease in oxygen concentration and an increase in ATP concentration can magnify the accumulation of NADH and consequently limit the metabolism of alcohol.
Alcohol metabolism shows steady state kinetics. Increased concentrations of alcohol have little or no effect on the reaction rate of alcohol metabolism. Therefore, the conversion of alcohol to acetaldehyde is not the limiting step in alcohol metabolism. The steady state kinetics of alcohol metabolism is a natural protective mechanism of the body, concerned with limiting the physiological effects of acetaldehyde and its by-products during alcohol metabolism. The composition of the present invention functions to eliminate the by-products of alcohol metabolism, rather than to stimulate the activity of ADH or ALDH.